As life expectancy in the US continues to rise, the maintenance of independence among older Americans has emerged as a major clinical and public health priority. Efficient and reliable locomotion, or the ability to move without assistance, is a fundamental feature of human functioning. Older people who lose mobility are less likely to remain in the community, have higher rates of morbidity, mortality, and hospitalizations and experience a poorer quality of life. Several studies have shown that regular physical activity improves physical performance, but definitive evidence showing that mobility disability can be prevented is lacking. A Phase 3 randomized, controlled trial is needed to fill this evidence gap. This application is a competitive renewal for the "Physical Exercise to Prevent Disability" pilot study, lay title "Lifestyle Interventions and Independence For Elders - LIFE" pilot study. The Data Safety Monitoring Board unanimously "determined that all pilot study benchmarks, including infrastructure, quality control, recruitment, adherence with the interventions, retention, safety, outcomes rates, outcomes definition refinement, and sample size estimates, were successfully achieved." We propose conducting a Phase 3, single-masked multicenter randomized controlled trial to compare a moderate-intensity physical activity program to a successful aging health education program in sedentary older persons who are at risk of disability. This trial will enable us to address the aims listed below. The primary aim is to assess the long-term effects of the proposed interventions on the primary outcome of major mobility disability, as operationalized by the inability to walk 400 m. Secondary aims focus on assessing the relative effects of the interventions on the following secondary outcomes: cognitive function;serious fall injuries;persistent mobility disability;the combined outcome of major mobility disability or death;disability in activities of daily living;and cost-effectiveness. Tertiary aims relate to assessing the relative effects of the interventions on (a) the combined outcome of mild cognitive impairment or dementia and (b) physical performance within pre-specified subgroups defined on the basis of ethnicity/race, gender and baseline physical performance;and (c) to explore time by intervention interactions on the SPPB score and 400 m walk speed endpoints. The proposed trial will provide definitive evidence regarding whether physical activity is effective and practical for preventing major mobility disability. Public Health Relevance: Should LIFE-M be successful, it would modify the current guidelines by providing a new indication for the physical activity intervention used in LIFE: the prevention or delay of major mobility disability. These results will have crucial implications for public health prevention in a rapidly aging society, and will fill an important gap in knowledge for practicing evidence-based geriatric medicine. The study will also yield valuable information concerning the efficacy and effectiveness of physical activity on a broad spectrum of other important health outcome, and will impact both clinical practice and public health policy, and will, therefore, benefit individuals and society.